Nano-safety update: scientists Invasively tested human for nanoparticle penetration, They were in for a surprise!

“Are they safe?” is the biggest and most nagging question about nanotechnology among the public. Almost everybody ask this, despite their level of knowledge and experience about nanotechnology. The truth is, perception about nanosafety is quite negative. Many “figure out” that because nanoparticles are very small, they can simply diffuse through the skin, get in to the bloodstream, go to your brain, kill important cells and make you terribly ill.

This also present an interesting scientific question. If nanoparticles can truly diffuse through the skin and harm our cells, using them in our everyday products is a risk that we should not take. However, the issue is, public opinion about nanosafety matters are not really based on nanotechnology safety assessments but based on fear and word of mouth. This is supported partly by relatively low amount of research carried out to investigate on the safety aspect of nanoparticles. Also the few research work that investigated on this matter wasn’t really communicated well to the public. In the scientific community, everybody wants to do something great with nanotechnology, and hope someone else will do the safety assessment. But this has not been the case in the past.

As ingestion and inhalation of nanoparticles is commonly avoided in the nanotechnology consumer products, skin remains as the most potential pathway for nanoparticles to get in to the body. The product area with highest concern is nanoparticle containing creams and lotions, because they are directly applied on to the skin.

Skin is the largest organ of the body and made up of three different layers with unique functionalities. The topmost layer, epidermis is the layer we can see. It protects the body from intruders and infections while working as a layer to limit evaporation of water in the body. Epidermis contains few layers of living cells and few dead ones. The outermost dead cell layer, stratum corneum, is the primary barrier layer in the skin. The layer is lipophilic and contains tightly bound cells. Dermis is the second layer of the skin. It contains tough connective tissues, hair follicles and sweat glands. The third layer, hypodermis is made of fat and connective tissues.

skin structure and nano particle penetration pathways

Fortunately nanosafety assessment and nanotoxicology research is catching up. In the recent years, there have been number of interesting studies on how most commonly used nanoparticles interact with our skin and affect body cells. Among the most tested nanoparticles are titanium dioxide nanoparticles are zinc oxide nanoparticles. Both are very popular as the main functional material in sunscreens to protect the wearer from harmful ultraviolet radiation from the sun. We have selected five, highly cited papers in the field of nanosafety of most commonly used nanoparticles on the skin creams and lotions and summarized the research findings.

Study on penetration of TiO2 nanoparticles through the skin by Makiko Fujii

Makiko and his group investigated penetration of TiO2 nanoparticles trough the dermatomed human skin. The size of the investigated particles are 1-35 nm with an alumina/silica coating. Interestingly they observe no penetration of the nanoparticles regardless of the top coating on the TiO2 nanoparticle. They further subjected the skin samples for scanning electron microscope imaging which revealed that TiO2 nanoparticles have only penetrated in to the vacant hair follicles. No evidence for penetration to deeper layers like dermis and viable epidermis was seen.

Investigation of TiO2 nanoparticle penetration through skin in sunscreen formulations

A group led by P. Moretto, investigated nano Titanium dioxide penetration through the human skin through in vitro tests on human skin and on human subjects. The nanoparticle size of the sunscreen formulations were found to be 20 nm and team observed very limited penetration through the skin and did not reach the living part of the skin. Diffusion of nanoparticles was only limited to upper layers of the stratum corneum. They did not observe any penetration through skin furrows or follicular openings in the skin.

TiO2 in various formulations tested on swine skin in vitro

The group led by T. Butz investigated the penetration of titanium dioxide nanoparticles in various cosmetic formulations. The tested TiO2 nanoparticles were having needle shape; a common morphology used in nanoparticle based sunscreens and lotions. The particles were in the range of 17 to 150 nm in diameter.  The test was carried out on swine skin which has a very unique resemblance to the human skin using a high sensitive measurement technique called spatially resolved ion beam analysis. The minimum detection level of this technique is as great at 1 particle/ square micrometer. The team observed the particles had limited diffusion in to the skin and no penetration into the living skin. The penetration mainly stopped at stratum corneum and minimally at stratum granulosum.

Study of TiO2 nanoparticle penetration through the skin by H. Gers-Barlag

Barlag and his team investigated the penetration parameters of Titanium dioxide nanoparticles through the human skin in vitro. The nanoparticles were in the size range of 10 to 100 nm. There were no coating on the surface of the nanoparticles. Results showed penetration of nanoparticles into the upper skin layers of the stratum corneum. Team couldn’t find any scientific evidence of further penetration. Team concluded that the topical application of TiO2 particles having diameters in 10 to 100 nm range would not provide a probable stage for any significant diffusion of nanoparticles.

TiO2 and ZnO penetration study through skin by Hemmerle

Research focused on both TiO2 and ZnO nanoparticle penetration through the skin primarily through the application of sunscreen emulsion. The analysis of the product revealed that the TiO2 particle sizes were in the range of 50 to 100 nm and ZnO particles were in the range of 20 to 200 nm. The experiments were conducted on human skin as an in vitro test. This team also couldn’t find couldn’t find any scientific evidence for the diffusion of nanoparticles any further from stratum corneum.

Summery

Like any other chemical, nanoparticle based products can also have a toxic effects if it can reach to the bloodstream. However, most of the research carried out on nanoparticles such as ZnO and TiO2 concludes that the skin is not a probable pathway for the above as they are stopped by the skin at its primary protective barrier stratum corneum. This prevents the nanoparticles from interacting with living cell layers. In summary, in contrast to the popular belief, there’s no evidence that the nanoparticles can penetrate the healthy, intact adult skin. However, ingestion and inhalation can still allow nanoparticles to gain access to circulation system. Like any other harmful chemicals, there are also nanoparticles that have proven toxicity profiles if mixed in to the blood stream.

Further reading

  1. Senzui, Mika, Toshiaki Tamura, Keiko Miura, Yoshiaki Ikarashi, Yoshiteru Watanabe, and Makiko Fujii. “Study on penetration of titanium dioxide (TiO2) nanoparticles into intact and damaged skin in vitro.”The Journal of toxicological sciences 35, no. 1 (2010): 107-113.

  2. Mavon, C. Miquel, O. Lejeune, B. Payre, and P. Moretto, “In vitro percutaneous absorption and in vivo stratum corneum distribution of an organic and a mineral sunscreen,” Skin Pharmacology and Physiology, vol. 20, no. 1, pp. 10–20, 2006.

  3. Menzel, T. Reinert, J. Vogt, and T. Butz, “Investigations of percutaneous uptake of ultrafine TiO2 particles at the high energy ion nanoprobe LIPSION,” Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms, vol. 219-220, no. 1-4, pp. 82–86, 2004.

  4. Pflücker, F., V. Wendel, H. Hohenberg, E. Gärtner, T. Will, S. Pfeiffer, R. Wepf, and H. Gers-Barlag. “The human stratum corneum layer: an effective barrier against dermal uptake of different forms of topically applied micronised titanium dioxide.” Skin Pharmacology and Physiology14, no. Suppl. 1 (2001): 92-97.

  5. DUSSERT, A‐, E. Gooris, and J. Hemmerle. “Characterization of the mineral content of a physical sunscreen emulsion and its distribution onto human stratum corneum.” International journal of cosmetic science19, no. 3 (1997): 119-129.

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